Significant progress has been made in clinicians' understanding of the molecular pathogenesis of BE, and the laboratory findings are beginning to lead to hypothesis-driven clinical studies; however, the following questions remain unanswered: (1) how can clinicians identify the persons most at risk for the development of esophageal adenocarcinoma, (2) what are the environmental gene interactions in esophageal carcinogenesis, and (3) can clinicians prevent the development of esophageal adenocarcinoma in the population at risk? As esophageal adenocarcinoma starts to reach epidemic proportions, further research in these areas is urgently required. With the advent of the genomic era and an explosion in studies in BE, significant progress can be made.